ABSTRACT Sickle cell disease (SCD) is recognized as a significant health disparity in the United States due to the number of patients affected, the paucity of available providers, disease stigmatization, and a lack of treatment options for affected individuals (4). In certain regions of the US, these issues are further worsened by a large percentage of affected patients living in rural regions with limited access to care, lower socioeconomic status, and fewer funding options (5, 6). South Carolina (SC) is a prime example of state that is tremendously under-resourced to treat individuals living with SCD. State-level engagement of pediatric hematologists, managed care organizations, patients, and community foundations resulted in formation of the South Carolina-Sickle Cell (SC2) statewide network designed to increase access to evidence-based care for all individuals living with SCD and to improve their clinical outcomes through access to a SCD medical home (Spoke) connected to a regional specialty care center (Hub). This approach harnesses the state?s resources to improve care for individuals with SCD, utilize the strengths of partnering hospital systems, and use a technology based approach to extend care to rural areas. This project, iSCENSC (Implementation of a Sickle Cell Enhanced Novel Care Network in South Carolina) is designed to evaluate intervention effectiveness for achieving full implementation of the SC2 network and to determine if the hub and spokes model of care increases access to quality care for individuals with SCD and produces findings sufficient to identify replicable methods for optimal care enrichment especially in rural populations. Specific Aims are: 1. Perform a systematic needs assessment in three target regions currently involved in SC2 (Midlands, Pee Dee and Lowcountry) to assess the gap between current and SCD best practices for adolescent and adult SCD patients and to identify care delivery issues associated with disease-specific care primary care, acute care management, and care coordination. 2: Engage all relevant stakeholders (patients/caregivers, providers, SC2 partners) to begin building capacity for the conduct and assessment of targeted interventions to increase implementation readiness within three SC regions and partnering health systems and to further inform Phase II implementation strategies. 3: Initiate comparative effectiveness study using an interrupted time series, multi-sector, multi-modal design including specific implementation intervention strategies. iSCENSC will be the first multilevel, multicenter implementation science study in adolescents and adults with SCD aiming to achieve the outcome of a statewide SCD network. We propose the first large study of barriers inhibiting adoption and use of NHLBI SCD Guideline and of effectiveness of dissemination and implementation strategies in closing existing guideline-to-practice gaps and reducing longstanding disparities in SCD treatment, policy, and funding support of SCD care delivery.